Eun Mi Song

Determinants of symptoms in gastroesophageal reflux disease: nonerosive reflux disease, symptomatic, and silent erosive reflux disease.

Background Nonerosive reflux disease (NERD) is detected frequently. Furthermore, as general checkups including endoscopy have become popular, silent erosive esophagitis (EE), which is defined as EE without the typical symptoms of gastroesophageal reflux disease (GERD), is also frequently encountered. We investigated the determinants of symptom presentation in symptomatic EE, NERD, and silent EE, which are representative GERD groups. Materials and methods Participants in a prospective health-screening cohort underwent upper endoscopy from June 2009 to September 2010. GERD was defined as heartburn and/or acid regurgitation at least weekly or EE by endoscopy. All participants were asked to complete a validated questionnaire, which included questions about gastrointestinal symptoms and the somatization symptom checklist (SSC). Results Among 4565 participants (men, 51.9%; mean age, 46.0±10.2 years), GERD was found in 678 participants (14.9%) and EE in 335 participants (7.3%). Each group of participants was classified into the following three categories: (i) symptomatic EE (n=38, 5.6%); (ii) NERD (n=343, 50.6%); and (iii) silent EE (n=297, 43.8%). Male sex and obesity were common predictors in both the symptomatic and the silent EE groups compared with the control group. Higher scores on the SSC [odds ratio (OR), 3.7; 95% confidence interval (CI), 1.8–7.8] and overlap of functional dyspepsia (OR, 35.4; 95% CI, 14.9–84.3) were predictors of symptomatic EE compared with asymptomatic EE. Symptomatic EE was more strongly associated with male sex (OR, 7.8; 95% CI, 2.9–20.9) than was NERD. Conclusion Somatization was the most important determinant of GERD symptoms. Silent EE was prevalent among participants with GERD, even though its natural history and clinical significance are unknown.

Forced Expiratory Volume in One Second as a Prognostic Factor in Advanced Non-small Cell Lung Cancer

Introduction: Reduced lung function is an important risk factor for lung cancer and increases surgical risk in patients with operable stages of lung cancer. Nevertheless, there have been few studies to reveal association of lung function with mortality in patients with advanced lung cancer. The aim of this study was to investigate whether low forced expiratory volume in 1 second (FEV1) is an independent predictor of mortality in patients with advanced lung cancer. Methods: Data were retrospectively collected from patients with non-small cell lung cancer of stage IIIB or IV and available spirometry at diagnosis of lung cancer. They had the last follow-up consecutively between April 2003 and July 2009 in a tertiary referral hospital. Results: Among a total of 156 patients, 118 died as of July 2009. Their mean age was 65 years; 115 (74%) were men. Mean FEV1 was 1.91 liters (79% of predicted). Seventy-one patients (46%) had adenocarcinoma, and 48 (31%) had squamous cell carcinoma. In a multivariate analysis using Cox regression model, independent prognostic factors were FEV1 less than 50% of predicted (hazard ratio [HR] = 2.704, 95% confidence interval [CI]: 1.516–4.823, p = 0.001), chemotherapy (HR = 0.311, 95% CI: 0.192–0.503, p < 0.001), adenocarcinoma (HR = 0.459, 95% CI: 0.300–0.701, p < 0.001), body mass index (HR = 0.921, 95% CI: 0.870–0.975, p = 0.005), and the presence of malignant pleural effusion (HR = 1.673, 95% CI: 1.102–2.540, p = 0.016). Conclusions: Reduced FEV1 is strongly associated with mortality in advanced non-small cell lung cancer.

Long-Term Outcomes of NSAID-Induced Small Intestinal Injury Assessed by Capsule Endoscopy in Korea: A Nationwide Multicenter Retrospective Study

Background/Aims We evaluated the long-term outcome and clinical course of patients of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injury by performing capsule endoscopy (CE). Methods A multicenter retrospective study was conducted using data collected from the CE nationwide database registry, which has been established since 2002. Results A total of 140 patients (87 males; mean age, 60.6±14.8 years) from the CE nationwide database registry (n=2,885) were diagnosed with NSAID-induced small intestinal injury and enrolled in our study. Forty-nine patients (35.0%) presented with a history of aspirin use and an additional 49 (35.0%) were taking NSAIDs without aspirin. The most prominent findings after performing CE were multiple ulcerations (n=82, 58.6%) and erosions or aphthae (n=32, 22.9%). During the follow-up period (mean, 15.9±19.0 months; range, 0 to 106 months), NSAID-induced small intestinal injury only recurred in six patients (4.3%). Older age and hypertension were positive predictive factors for recurrence. Conclusions These results suggest that the recurrence of NSAID-induced small bowel injury was not frequent in the presence of conservative treatment. Therefore, the initial diagnosis using CE and the medication history are important.

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

Purpose Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). Materials and Methods Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. Results AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p<0.001; 95% CI, 0.95-1.00). The summation of sensitivity and specificity was highest at the initial cTnT value of 0.35 ng/mL (sensitivity, 0.95; specificity, 0.97). Survival analysis showed a statistically significant difference in all-cause and cardiovascular mortalities for the group with an initial cTnT ≥0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. Conclusion Because ESRD patients with an initial cTnT concentration ≥0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are ≥0.35 ng/mL.

Elevated C-reactive protein level during clinical remission can predict poor outcomes in patients with Crohn’s disease

Intestinal inflammation and mucosal damage in Crohn’s disease (CD) are believed to progress even during clinical remission. We investigated the long-term prognosis of CD patients in clinical remission according to serum C-reactive protein (CRP) levels. This study included 339 CD patients in clinical remission (Crohn’s disease activity index < 150) for more than 6 months between January 2008 and December 2010. Clinical outcomes were compared between patients with normal and elevated CRP levels during clinical remission. During clinical remission, 150 patients had normal CRP consistently and 189 had elevated CRP at least once. During follow-up (median, 7.9 years [interquartile range, 6.8–8.0]), the Kaplan–Meier analysis with the log-rank test showed that normal CRP group had a longer CD-related hospitalization-free survival (P = 0.007) and a longer CD-related intestinal resection-free survival (P = 0.046) than elevated CRP group. In multivariate analysis, elevated CRP was significantly and independently associated with an increased risk of subsequent CD-related hospitalization (adjusted hazard ratio [aHR] 1.787, 95% confidence interval [CI]: 1.245–2.565, P = 0.002) and of subsequent CD-related intestinal resection (aHR 1.726, 95% CI: 1.003–2.969, P = 0.049). The most common reason for CD-related hospitalization was penetrating complications (35.6%). Even when CD patients are in clinical remission, elevated CRP is significantly associated with subsequent CD-related hospitalization and CD-related intestinal resection during follow-up. CD patients in clinical remission but elevated CRP should receive more careful attention and timely interventions to improve long-term outcomes.

Sa1899 Risk Factors and Clinical Outcomes Associated With Cytomegalovirus Colitis in Patients With Acute Severe Ulcerative Colitis

BACKGROUND Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC. METHODS We retrospectively analyzed patients with ASUC from 2011 to 2014 according to the criteria of Truelove and Witts. CMV colitis was diagnosed by histopathological and/or immunohistochemical analysis of tissue samples. The risk factors for CMV colitis were investigated and clinical outcomes were assessed using the rate of rescue therapy and colectomy. RESULTS Of 149 patients with ASUC, 50 (33.6%) were diagnosed with CMV colitis. During admission, 16 of 149 patients (10.7%) underwent colectomy: 7 of 50 (14.0%) in the ASUC-CMV group versus 9 of 99 (9.1%) in the ASUC-only group (P = 0.364). The need for rescue therapy was 2.28-fold higher in the ASUC-CMV group than in the ASUC-only group in multivariate analysis (95% confidence interval, 1.10-4.72). Multivariate analysis also revealed that recent use of high-dose steroids (odds ratio, 3.30; 95% confidence interval, 1.33-8.19) and a higher Mayo score (odds ratio, 1.58; 95% confidence interval, 1.05-2.38) were risk factors for CMV colitis. CONCLUSIONS CMV colitis often occurs in ASUC, particularly in patients who have recently been treated with high-dose steroids and have a higher Mayo score on admission. Patients with ASUC and CMV colitis seem to have a poorer prognosis, as indicated by the greater need for rescue therapy.

Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn’s disease

AIM To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn’s disease (CD) patients in Asian countries. METHODS IFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician’s judgment of patients’ clinical status at enrollment. The impact of concomitant immunomodulators was also investigated. RESULTS This study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083). CONCLUSION IFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice.

Clinical outcomes of colorectal endoscopic submucosal dissection and risk factors associated with piecemeal resection

BACKGROUND/AIMS We aimed to investigate the factors associated with piecemeal resection of colorectal neoplasia (CRN), in spite of endoscopic submucosal dissection (ESD). MATERIALS AND METHODS We analyzed the retrospective data for colorectal ESD cases from January 2005 to April 2014. We also reviewed the piecemeal endoscopic mucosal resection (EMR) for CRNs ≥20 mm, performed over the same period. RESULTS En bloc resection was possible in 648 (85.7%) of 756 lesions in 740 patients. Multivariate analysis showed that hybrid ESD (odds ratio (OR), 29.07; 95% confidence interval (CI), 15.46-54.65; p<0.01) and mild or severe submucosal fibrosis (OR, 3.62; 95% CI, 1.94-6.76; p<0.01) were independently associated with piecemeal ESD. The en bloc ESD group showed higher histologic complete resection rate than the piecemeal ESD group (80.4% vs. 56.5%; p<0.01), and the piecemeal ESD group showed higher recurrence rate than in the en bloc ESD group (5.6% [4/72] vs. 0.7% [3/450]; p<0.01). Overall recurrence rate was 1.3% (7/522). CONCLUSION Hybrid ESD and submucosal fibrosis are independently associated with piecemeal ESD. Piecemeal ESD cases recurred more frequently than en bloc ESD cases.

The Therapeutic Efficacy of Tonsil-derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-induced Acute Murine Colitis Model

Background/Aims Mesenchymal stem cells (MSCs) are multipotent progenitor cells currently under investigation for its efficacy as the treatment for inflammatory bowel disease. In this study, we evaluated the efficacy of tonsil-derived mesenchymal stem cells (T-MSCs) as a novel source of mesenchymal stem cells and traced their localization in a murine model of acute colitis induced by dextran sulfate sodium (DSS). Methods C57BL/6 mice were randomly assigned to the following three groups: the normal control group, DSS colitis group (DSS+phosphate buffered saline), and T-MSC group (DSS+T-MSCs, 1×106). The severity of colitis was assessed by determining the severity of symptoms of colitis, colon length, histopathologic grade, and levels of inflammatory cytokines. T-MSCs labeled with PKH26 were traced in vivo. Results The T-MSC group, compared with the DSS colitis group, showed a significantly lower disease activity index (11.3±1.5 vs. 8.3±1.9, p=0.015) at sacrifice and less reduction of body weight (-17.1±5.0% vs. -8.1±6.9%, p=0.049). In the T-MSC group, the histologic colitis score was significantly decreased compared with the DSS colitis group (22.6±3.8 vs. 17.0±3.4, p=0.039). IL-6 and IL-1β, the pro-inflammatory cytokines, were also significantly reduced after a treatment with T-MSCs. In vivo tracking revealed no PKH26-labelled T-MSCs in the colonic tissue of mice with acute colitis. Conclusions In the acute colitis model, we demonstrated that the administration of T-MSCs ameliorates inflammatory symptoms and histology. Moreover, the anti-inflammatory activities of T-MSCs were independent of gut homing.

Therapeutic potential of tonsil-derived mesenchymal stem cells in dextran sulfate sodium-induced experimental murine colitis

The therapeutic potential of tonsil-derived mesenchymal stem cells (TMSC) prepared from human tonsillar tissue has been studied in animal models for several diseases such as hepatic injury, hypoparathyroidism, diabetes and muscle dystrophy. In this study, we examined the therapeutic effects of TMSC in a dextran sulfate sodium (DSS)-induced colitis model. TMSC were injected in DSS-induced colitis mice via intraperitoneal injection twice (TMSC[x2]) or four times (TMSC[x4]). Control mice were injected with either phosphate-buffered saline or human embryonic kidney 293 cells. Body weight, stool condition and disease activity index (DAI) were examined daily. Colon length, histologic grading, and mRNA expression of pro-inflammatory cytokines, interleukin 1β (IL-1β), IL-6, IL-17 and tumor necrosis factor α, and anti-inflammatory cytokines, IL-10, IL-11 and IL-13, were also measured. Our results showed a significant improvement in survival rates and body weight gain in colitis mice injected with TMSC[x2] or TMSC[x4]. Injection with TMSC also significantly decreased DAI scores throughout the experimental period; at the end of experiment, almost complete reversal of DAI scores to normal was found in colitis mice treated with TMSC[x4]. Colon length was also significantly recovered in colitis mice treated with TMSC[x4]. However, histopathological alterations induced by DSS treatment were not apparently improved by injection with TMSC. Finally, treatment with TMSC[x4] significantly reversed the mRNA levels of IL-1β and IL-6, although expression of all pro-inflammatory cytokines tested was induced in colitis mice. Under our experimental conditions, however, no apparent alterations in the mRNA levels of all the anti-inflammatory cytokines tested were found. In conclusion, our findings demonstrate that multiple injections with TMSC produced a therapeutic effect in a mouse model of DSS-induced colitis.